The Role of RNA interference in the induction of immune responses. Our work will allow us to understand a new means by which to alert the immune system to the presence of cancer cells using a new technology called RNA interference. This will hopefully lead to new investment in biotechnology products based on RNA interference, improved treatments for cancers and better health for Australians
Engineered Polymer Nanoparticles: A Potent Weapon Against Cancer. Cervical cancer is the commonest cause of cancer death in women under the age of 50 worldwide, the 8th most common cancer among women in Australia, and is the leading cause of cancer death in Aboriginal women. While a vaccine is available to prevent HPV-mediated disease, it would not impact upon death rates for at least 25 years. The systemic delivery of RNAi offers to best opportunity to solve this problem. The delivery devices w ....Engineered Polymer Nanoparticles: A Potent Weapon Against Cancer. Cervical cancer is the commonest cause of cancer death in women under the age of 50 worldwide, the 8th most common cancer among women in Australia, and is the leading cause of cancer death in Aboriginal women. While a vaccine is available to prevent HPV-mediated disease, it would not impact upon death rates for at least 25 years. The systemic delivery of RNAi offers to best opportunity to solve this problem. The delivery devices will be designed with precision and function to meet the delivery needs in vivo. These polymer structures will be suitable for use in drug and gene delivery providing Australian products with advanced features and capabilities, significantly improving product performance.Read moreRead less
Noncanonical epitope recognition by CD8+ T lymphocytes. This proposed research program will provide significant fundamental insight in the areas of immunology and vaccine design. Vaccines for many diseases remain elusive, and this project aims to improve our understanding of the precise regions within pathogens that are the targets for the killer T cells of the immune system. These regions, called epitopes, are likely to be key ingredients in many future vaccines. Although immunologists have gat ....Noncanonical epitope recognition by CD8+ T lymphocytes. This proposed research program will provide significant fundamental insight in the areas of immunology and vaccine design. Vaccines for many diseases remain elusive, and this project aims to improve our understanding of the precise regions within pathogens that are the targets for the killer T cells of the immune system. These regions, called epitopes, are likely to be key ingredients in many future vaccines. Although immunologists have gathered much information about such epitopes, recent studies have shown that some unexpected regions of pathogens are targets for killer T cells. This project will break new ground by utilising unbiased procedures to assess the relative contribution of these noncanonical epitopes to immunity.Read moreRead less
New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based intervent ....New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based interventions and vaccines that protect the gut and lung from infectious and inflammatory issues. The harnessing of effective immune responses to control such challenges, are of enormous fundamental and long-standing biological interest, and are amongst the most important areas of current scientific research.Read moreRead less
Structure and function of novel macrophage proteins using high throughput crystallography. We will combine the cutting edge technologies of microarray analysis and high throughput crystallography in an innovative approach to study the structure and function of important and uncharacterised macrophage proteins. Our strategy for targeting novel macrophage proteins will maximise the success rate of structure determination, while at the same time focusing our efforts on proteins that are important i ....Structure and function of novel macrophage proteins using high throughput crystallography. We will combine the cutting edge technologies of microarray analysis and high throughput crystallography in an innovative approach to study the structure and function of important and uncharacterised macrophage proteins. Our strategy for targeting novel macrophage proteins will maximise the success rate of structure determination, while at the same time focusing our efforts on proteins that are important in macrophage biology. Structures of the novel proteins will underpin functional analysis at a molecular level and could represent a basis for inhibitor design should the proteins ultimately be shown to be therapeutic targets.Read moreRead less
Investigating the molecular basis of T-cell receptor cross-reactivity. This project will explore the basis of unexpected immune reactions whereby the immune system mistakes one molecular structure for another, a phenomenon known as cross-reactivity. This project will examine how often this is due to molecular mimicry, potentially explaining why immune T cells sometimes react inappropriately to different agents.
Understanding the molecular mechanisms regulating neuronal fusion. Neurons are tightly connected individual cells that communicate through chemical and electrical signals, and this project aims to discover the key molecules that allow these cells to remain as individual units without fusing with each other. The nervous system, unlike other tissues, is made of discrete individual cells, connected by chemical and electrical synapses but not by cytoplasmic continuity. However, how this is achieved ....Understanding the molecular mechanisms regulating neuronal fusion. Neurons are tightly connected individual cells that communicate through chemical and electrical signals, and this project aims to discover the key molecules that allow these cells to remain as individual units without fusing with each other. The nervous system, unlike other tissues, is made of discrete individual cells, connected by chemical and electrical synapses but not by cytoplasmic continuity. However, how this is achieved and how neurons maintain their individuality during development, remodelling and ageing is unknown. The project aims to address this gap using a genetic approach and the nematode Caenorhabditis elegans as an experimental system. The results may provide insights into how the nervous system develops and functions.Read moreRead less
Interactions between phenome and genome at developing CNS synapses during synaptic refinement. Activity-dependent changes in synaptic transmission are vital to development and function of central neuronal networks. However, the critical factors regulating developmental changes in synaptic signals remain largely unknown. We will correlate functional changes in synaptic responses at glutamate-releasing synapses with changes in glutamate receptor composition at a critical period during developmen ....Interactions between phenome and genome at developing CNS synapses during synaptic refinement. Activity-dependent changes in synaptic transmission are vital to development and function of central neuronal networks. However, the critical factors regulating developmental changes in synaptic signals remain largely unknown. We will correlate functional changes in synaptic responses at glutamate-releasing synapses with changes in glutamate receptor composition at a critical period during development, test whether synaptic activation of receptors is required for these changes and define the pattern of activity-dependent changes in gene expression necessary for developmental changes in synaptic transmission. Understanding this interaction between synaptic phenome and activity-dependent genomic expression will expand our understanding of brain development and function.Read moreRead less
Dissecting The Great Ophthalmic Masquerade: The Global Giant Cell Arteritis Genomics Consortium.
Funder
National Health and Medical Research Council
Funding Amount
$583,269.00
Summary
Giant cell arteritis (GCA) is the most common form of vasculitis in people over 50 years of age. If untreated it can cause catastrophic complications including blindness, though this can be prevented if treated early. Although there is clear evidence for a role of genetic factors in GCA, these have been little studied. We have established an Australian-led International consortium, with clinical, basic science and statistical expertise to thoroughly investigate this devastating disease.
Development of novel reagents that specifically counteract EphA4 to enhance axonal regeneration. This project will examine the role of EphA4, an important guidance protein, in neural cell regeneration. The goal is to understand the signalling mechanisms that inhibit regeneration in the central nervous system and to develop novel biological agents to overcome these processes and promote functional recovery after nervous system injury or disease.